The functional analysis of Erc gene encoding GPI anchor protein

编码GPI锚定蛋白的Erc基因的功能分析

基本信息

批准号：
18500330
负责人：
ZHANG Danqing
金额：
$ 2.63万
依托单位：
Juntendo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18500330/
关键词：
Erc Mesothelin gene Tsc2 gene GPI anchor protein knockout mouse Carcinogenesis Erc遺伝子

项目摘要

The Erc (expressed in renal carcinoma) was identified as an inducible gene during the renal carcinogenesis of the Eker (Tsc2 mutant) rat and is a homologue of the human Mesothelin gene. Erc is also overexpressed in the renal carcinoma cell line of the Tsc2 knockout (KO) mouse. To elucidate functional importance of Erc in renal carcinogenesis as well as in mesothelioma, we have performed genetic cross experiments between Tsc2 KO and Erc KO mice. Then we examined influence of the Erc genotype on the development of renal carcinomas in the Tsc2 hetero-mutant mouse. In 32% of male and 20% of female Tsc2 hetero-mutant mice with wild-type Erc, renal carcinomas with a diameter ranging from 4 to 30mm were developed by the age of 18 months. In contrast, all of the renal carcinomas in Tsc2 hetero-mutant mice with Erc homo-mutation had a diameter equal to or less than 2mm. There was no remarkable difference in the size of renal tumors between Tsc2 hetero-/Erc hetero-mutant and Tsc2 hetero-mutant/Erc wild-type mice. These results suggest that Erc may play an important role for tumor proliferation. In addition, we established Tsc2/Erc-deficient renal carcinoma cell lines and then transferred Erc-expression system into them. Adhesion of cell lines to the collagen-coated plate became stronger by overexpression of Erc protein. On the other hand, cell adhesive property was deteriorated when Erc expression was inhibited by RNA interference, suggesting that Erc has a role in the cell-substrate adhesion. Now we are further investigating in vivo function of Erc by implanting the renal carcinoma cell lines into the nude mouse.

在Eker（TSC2突变体）大鼠的肾癌发生期间，ERC（在肾癌中表达）被确定为诱导基因，是人间皮素基因的同源物。 ERC在TSC2敲除（KO）小鼠的肾癌细胞系中也过表达。为了阐明ERC在肾癌发生以及间皮瘤中的功能重要性，我们在TSC2 KO和ERC KO小鼠之间进行了遗传跨实验。然后，我们检查了ERC基因型对TSC2异晶体小鼠肾癌发展的影响。在32％的雄性和20％的雌性TSC2异质杂种小鼠中，肾脏癌的直径为4至30mm，到18个月大。相比之下，ERC同型的TSC2异质突变小鼠中的所有肾癌的直径等于或小于2mm。 TSC2杂音 - /ERC杂种突变剂和TSC2杂种/ERC野生型小鼠之间的肾脏肿瘤大小没有显着差异。这些结果表明，ERC可能对肿瘤增殖起重要作用。此外，我们建立了TSC2/ERC缺陷型肾癌细胞系，然后将ERC表达系统转移到其中。通过ERC蛋白的过表达，细胞系对胶原蛋白涂层板的粘附变得更强。另一方面，当RNA干扰抑制ERC表达时，细胞粘附特性会恶化，这表明ERC在细胞基底粘附中起作用。现在，我们通过将肾癌细胞系植入裸鼠，进一步研究ERC的体内功能。